Pneumatically coupled direct drive fluid control system and process

ABSTRACT

A fluid control system for delivery of a liquid includes a pneumatic drive that incorporates a linear actuator to effect known volume changes in a gas reservoir. The gas reservoir is in fluid communication with a gas-side reservoir that is separated from a fluid-side reservoir by a flexible membrane. Movement of the linear actuator effects positive or negative volume differences on the gas in the gas-side reservoir, resulting in a decrease or increase in pressure of the gas that is transmitted to the fluid-side reservoir to draw fluid, primarily liquid, in from a source or deliver liquid out to a sink. In another aspect, a mechanism is provided for the detection and elimination of air bubbles in the fluid path.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. patent applicationSer. No. 14/285,278 filed May 22, 2014, which, in turn, claims thebenefit under 35 U.S.C. § 119(e) of U.S. Provisional Patent ApplicationNo. 61/826,863, filed May 23, 2013. Each of the aforementionedapplications is incorporated by reference herein in its entirety.

BACKGROUND

Fluid flow control is an essential part of medical devices such asintravenous infusion pumps and enteral feeding systems. These fluid flowcontrol systems must meet a complex and conflicting set of requirements,such as broad flow rate range, wide ranging fluid viscosity, inevitablepresence of harmful amounts of gas, changing source pressure, changingpatient pressure, variable patient line resistance, and a wide range oftubing configurations.

Reliability and ability to detect fault conditions are critical featuresof such flow control devices. Low acquisition and maintenance costs areimportant characteristics also.

The usability of the system is vitally important, as it impacts theworkflow of caregivers, which has a strong, but indirect, impact on thequality of patient care. This usability includes ease of loading thesterile tubing set, the need for attention from the caregiver during thefluid delivery period, and attending to unnecessary alarm conditions.

Conventional fluid control or pumping mechanisms suffer from anunfavorable tradeoff between sophistication and complexity. The addedcomplexity of many modern systems has led to a lack of reliability,resulting in product performance failures, high levels of maintenance,product recalls by regulatory agencies, and documented high rates ofpatient harm.

One of the earlier types of fluid pump, as marketed by Harvard ApparatusCompany and as replicated in the market hundreds of times thereafter, isa syringe pump. In a syringe pump, fluid is contained within a commonlyfound glass or plastic syringe, manufactured with a well-specifieddiameter and stroke length. These are the same syringes that are used toprovide manual injections of sterile fluid. The piston of the syringe issecurely held and, usually with a lead screw mechanism, the piston isadvanced in carefully timed steps of a motor. Each step of the motorexpresses a known amount of liquid out of the syringe and into a linegoing to the vasculature of the patient. The syringe pump offers a verysimple mechanism and an extraordinarily simple control system,consisting of a timer circuit, set by the desired fluid flow rate. Forceand position sensors are often added to provide feedback regardingocclusions, misloading, and end of infusion. The syringe pump design isinherently limited, however, by the relatively small size of thesyringe, in the amount of fluid infused and in the maximum fluid flowrate, so this design does not satisfy the needs of many clinicalapplications. Ironically, at the very small volumes and flow rates, thesyringe pump suffers from a discontinuity of fluid flow, based on thehigh static friction of the syringe. Very small movements of the drivemotor do not necessarily translate into movement of the piston anddelivery of fluid; it may take multiple motor steps and multiple timeintervals before the piston actually delivers fluid to the patient. Longdelay periods between delivery are not desirable clinically. A furtherdeficiency in the syringe pump is the improper impedance match with thepatient's vasculature; the syringe pump motor drive is equipped with amotor that is capable of reliably meeting the maximum torque foreseen bythe system. This powerful motor is also geared down such that very lowdisplacements can be achieved, giving the pump the ability to deliver atlow flow rates. The combination of the powerful motor and the gearing,however, allows the syringe drive to generate fluid pressures that arefar in excess of those needed to safely infuse a fluid into thevasculature of a patient. The consequence of this potentially highpressure output is that harmful levels of fluid pressure can be appliedto the patient, with deleterious effects, especially in the event of anextravasation of the infusion catheter or the creation of a bolus uponrelease of a temporary occlusion.

Variations of the syringe pump are to be found in the form of areciprocating piston that can draw from a fluid bag or vented bottle.Such devices, as found with the Abbott/Hospira Plum™ infusion device,overcome the volume limitation of a syringe pump. Added complexity forvalving serves to increase cost and reduce reliability. A large volumepump, because of its multiple fluid connections and air spaces, createsan environment, not found with syringe pumps, for the introduction ofharmful air bubbles, which must be detected and accommodated. Thesereciprocating piston pumps still retain the disadvantage of impedancemismatch described above for syringe pumps.

The most common form of infusion pump is the peristaltic pump, whereuponfingers or rollers occlude a section of flexible tubing in peristalticfashion, expressing fluid out the tube toward the patient. Thismechanism provides the simplest configuration to carry the sterile fluidin the form a simple flexible tube. The peristaltic pump suffers thesame impedance mismatch fate as the syringe pump, because the forcesrequired to faithfully occlude a portion of the flexible tube are great,allowing the pump to generate harmfully high infusion pressures. Thispotentially high pressure can be mitigated through the use of forcesensors on the tubing, adding complexity and cost. The problem with airingress to the patient is the same as with the reciprocating piston pumpdescribed above. The peristaltic pump introduced a new problem relatedto fluid flow accuracy, since the amount of fluid expressed to thepatient is entirely dependent on the interior diameter of the fluidtubing in its uncompressed state. In fact the surface area error is asquare law function of the error in the diameter, so a 10% error in thediameter would yield an unacceptable 21% (1.1²) error in the volumeexpressed to the patient. Unfortunately, there are two very commonevents that can reduce the effective diameter of the tubing: one is thefatigue of the tubing as it is repeatedly worked by the peristalticmechanism and the other is the failure of the tubing to refillcompletely due to low flow from the fluid source.

There is another class of pumps providing single flow rates using aconstant force spring, membrane, or gas reaction pushing fluid against afixed, calibrated resistance. These devices do not provide theprogrammable variation of flow rate needed for most clinicalapplications.

One variation of the reciprocal piston pump was designed and marketed byFluidSense Corporation of Newburyport, Mass. It used a flexible membraneconnected to a spring-loaded piston on one side and sterile fluid on theother. A low cracking pressure passive inlet valve and an activelyoperated momentary outlet valve provided for a pumping action if thespring loaded piston were “cocked” back to load the spring, providing apositive fluid force. A highly sensitive linear encoder was used towatch the position of the spring-loaded piston, providing information onthe fluid pressure and volume. This design allowed for a simplified andmore sensitive pump mechanism, but the flow was intermittent with theaction of each pulse of the outlet valve and the driving pressure variedfrom 3 to 7 PSIg, higher than necessary for most clinical applications.It also suffered from the introduction of air bubbles, as with all largevolume pumping systems.

Programmable infusion devices, as opposed to single rate deliverysystems, all suffer from two effects of electromechanical complexity.First, there are usually tight mechanical tolerances which can bedisturbed by shock, vibration, temperature shifts, and aging. Infusionpumps are often out of their performance specifications, sometimesintermittently, making troubleshooting very expensive and difficult.Secondly, these complex mechanisms are often difficult to disinfect.Customers have only recently become sensitized to the extremely highimportance of disinfecting infusion pumps and other medical devices.Cross contamination of patients is one of the top healthcare issues inthe acute care environment.

Another particular problem that patients and caregivers face with greatregularly is the presence of air bubbles in the fluid path. Conventionalinfusion pumps observe a segment of tubing via an ultrasonic or opticaldetector circuit. They reliably detect bubbles with high sensitivity.Unfortunately, the specificity of these sensors is low, so false alarmsare commonplace. When these bubbles are detected, three bad thingshappen. First, the pump goes into an alarm condition and fluid flow tothe patient is halted, which can often cause harm to the patient bywithholding needed medication. Second, the alarm at the bedside causessignificant distress to the patient and the patient's family. Third, thealarm disrupts the nurse's workflow, taking time away from otherpatients and directing the nurse's attention toward the infusion pumpand away from the patient.

Air eliminating filters are commonly found in infusion therapyadministration sets. These filters fail to solve the problems identifiedabove, because these filters do not function properly when exposed tonegative gauge pressures if they are positioned proximal to the infusionpump. If these filters are placed below the infusion pump, then there isno way for the pump to verify that these filters are in place, so thealarms must still stay active. These filters must also incorporatehydrophilic filters, which are not compatible with certain medicalfluids, such as whole blood.

SUMMARY OF THE INVENTION

The present invention relates to a fluid control system implemented as apneumatically coupled direct drive. The system is reliable, tolerant ofchanging conditions, and sensitive to conditions that prevent theaccurate delivery of fluid. The system provides a simple actuatingmechanism coupled with a low-pressure, closed loop control system, whichovercomes the limitations of prior art systems described above.

The pneumatic drive of the fluid control system incorporates a linearactuator that interfaces with a gas reservoir to effect known volumechanges in the gas reservoir. In one embodiment, the linear actuatorcomprises a drive motor coupled to a mechanism that provides linearmotion to push or pull a reciprocating element, such as a bellows or apiston, by known linear increments. The reciprocating element translatesbi-directionally in one dimension and has a fixed, known cross-sectionalarea, for example, in a plane orthogonal to the direction oftranslation. Thus, translation by a known distance results in a knownvolume change within the gas reservoir. The reciprocating elementinterfaces with a gas, typically air, in the gas reservoir such thattranslation of the reciprocating element increases or decreases the gasvolume in the gas reservoir. The motor can be moved in either directionto increase or decrease the gas volume. A pressure sensor in the gasreservoir senses the gas pressure therein. A vent valve to ambient isalso provided in the gas reservoir.

The gas reservoir is in fluid communication with a divided fluidchamber. The fluid chamber is separated by a flexible membrane into agas-side reservoir and a fluid-side reservoir. The gas in the gas-sidereservoir is in fluid communication with the gas in the gas reservoir ofthe linear actuator. The fluid-side reservoir is filled primarily with aliquid, such as medication or a feeding solution for delivery to thevasculature of a patient. Reciprocal motion of the reciprocatingelement, e.g., the piston or bellows, under control of the drive motor,imposes positive or negative volume differences on the gas in thegas-side reservoir, which results in a decrease or an increase in thepressure of the gas. This in turn causes a flexing of the membrane,which communicates the pressure difference to any fluid in thefluid-side reservoir. Passive inlet and outlet check valves are disposedalong the fluid flow path through the fluid-side reservoir. The inletand outlet check valves open in response to the pressure changes in thefluid to create a unidirectional pumping action to move the fluid inthrough the inlet check valve and subsequently out through the outletcheck valve.

The system includes a controller that operates the pneumatic drive. Thecontroller is operable to control delivery of liquid to the fluid sinkby determining a volume of liquid to be delivered as the differencebetween a target volume of liquid to be delivered and a volume of liquidalready delivered and operating the pneumatic drive in incrementscalculated to deliver the volume of liquid to be delivered. Thecontroller is operable to calculate the volume of liquid to be deliveredat successive time intervals and update the volume of liquid alreadydelivered after each calculation of the volume of liquid alreadydelivered.

The controller receives sensed pressure data from the pressure sensor atregular time intervals, including before and after a controlled movementof the pneumatic drive, and compares the pressure data to a known changein gas volume resulting from said controlled movement. The controllercalculates a volume of gas based on the pressure data and the knownchange in gas volume based on an ideal gas law relationship between thesensed pressure data and the known gas volume.

The controller is also operable to determine pressure trends indicativeof various conditions, such as an impedance or a resistance in the fluidflow path from the fluid source or to the fluid sink. The impedance orthe resistance in the fluid source can be indicative of, for example, anocclusion in a line on the fluid flow path, an amount of liquidremaining in the fluid source, a viscous liquid at the fluid source, orthe presence of a syringe. The impedance or the resistance in the fluidflow path to the fluid sink can be indicative of, for example, anocclusion in a line on the fluid flow path or a disconnected connectionto the fluid sink.

In another aspect, the fluid control system incorporates an airdetection and active air elimination mechanism that has improveddetection specificity and is operable to eliminate an unlimited amountof air so as to avoid the negative aspects of air bubbles. The airelimination mechanism includes a hydrophobic filter material thatprevents passage of liquid and a one way valve through which air canleave the system.

DESCRIPTION OF THE DRAWINGS

The invention will be more fully understood form the following detaileddescription taken in conjunction with the accompanying drawings inwhich:

FIG. 1 is a schematic block diagram of one embodiment of a fluid controlsystem;

FIG. 2 is a schematic block diagram of a controller for use in the fluidcontrol system of FIG. 1;

FIG. 3 is a schematic diagram illustrating positions of a linearactuator of the fluid control system at various states in a pumpingcycle;

FIG. 4a is a schematic diagram of a pumping chamber of FIG. 1 includingan air elimination system;

FIG. 4b is an expanded schematic diagram of the air elimination systemof FIG. 4 a;

FIG. 5a is an isometric view of one embodiment of a fluid administrationset illustrating a cassette and a housing;

FIG. 5b is an isometric view of FIG. 5a illustrating the cassetteinserted within the housing;

FIG. 6 is an exploded view of the cassette of FIG. 5 a;

FIG. 7a is a cross-sectional view of the cassette;

FIG. 7b is a further cross-sectional view of the cassette;

FIG. 8 is a cross-sectional view of an inlet valve in the cassette;

FIG. 9 is a cross-sectional view of an air valve in the cassette;

FIGS. 10a and 10b are isometric views illustrating an air filter for anair elimination system used with the cassette;

FIG. 11a is an isometric view of a by-pass valve assembly used with thecassette;

FIG. 11b is an isometric view of the by-pass valve assembly in a closedposition;

FIG. 12a is an exploded view of the cassette illustrating a pneumaticpathway within the cassette;

FIG. 12b is a top view of the cassette body illustrate the pneumaticpathway;

FIG. 13 is a schematic block diagram of an embodiment of a failsafecircuit incorporating an additional vent valve;

FIG. 14 is a graph of a pressure response to a known decrease in gasvolume;

FIG. 15 is a graph of a pressure response to a known increase in gasvolume;

FIG. 16 depicts the change in pressure when a pressure-activated one wayvalve is opened with increasing pressure;

FIG. 17 is a schematic graph of volume vs. time to illustrate flowcalculations made during fluid delivery;

FIG. 18 depicts the change in pressure when the sink pressure changes;

FIG. 19 depicts the change in pressure when the sink impedance changes;

FIG. 20 depicts the differentiation between pressure and impedancechanges in the sink;

FIG. 21 depicts pressure responses over time during various conditionsduring a fill cycle;

FIG. 22 depicts pressure responses over time during various conditionsduring a delivery cycle; and

FIG. 23 depicts a pressure response over time during a portion of afluid delivery stroke.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 depicts a schematic block diagram for one embodiment of a fluidcontrol system 100. The system incorporates a pneumatic drive 101 thatinterfaces with a fluid administration set 102 by which controlledamounts of fluid are withdrawn from a fluid source 130 and delivered toa fluid sink 140, such as the vasculature of a patient. The fluidcontrol system can be embodied as a stand-alone pumping system or as asubassembly that is coupled to another pumping system that includesother components, such as a user interface, drug safety software, powersupply, chassis, etc.

The fluid source 130 may be, e.g., a fluid contained within a flexiblebag, a vented bottle, or a liquid filled syringe. The fluid flows on aflow path 131 through a pumping chamber 170, which is a rigid body orhousing having a fixed volume. The chamber is divided by a flexiblemembrane 175 that is impermeable to gas or liquid into a gas-sidechamber 171 and a fluid-side chamber 172. The flexible membrane 175 issealingly fastened about its periphery within the chamber 170, but isotherwise free to move without restriction. Gas pressure within thegas-side chamber 171 imposes the same pressure within the fluid-sidechamber 172. There is effectively no pressure differential across theflexible membrane 175. Pressure changes in the gas-side chamber aredirectly communicated to the fluid-side chamber via the flexiblemembrane and vice versa.

The fluid-side chamber 172 is disposed on the fluid flow path 131 and isin fluid communication with the fluid source 130 via an inlet valve 135.The fluid side chamber 172 is also in fluid communication with the fluidsink 140 via an outlet valve 145. The inlet valve and outlet valve eachare passively operated one-way check valves and only open when thepressure differential between the upstream fluid and downstream fluidreaches a predetermined cracking pressure. The inlet valve 135 andoutlet valve 145 each are normally closed to flow and require arelatively high differential pressure to open them in a forwarddirection. No practical amount of differential pressure can open them inthe reverse direction. In one embodiment, suitable as a medical infusionpump, both valves 135, 145 are selected to have a relatively highcracking pressure, on the order of 1 PSId. The particular crackingpressure depends on the application, as would be appreciated by one ofskill in the art.

The system also includes a pneumatic drive that is coupled to thegas-side chamber 171 to effect known incremental positive or negativevolume changes that in turn cause positive or negative pressure changesin the gas-side chamber that are communicated to the fluid-side chamber172. In one embodiment, the pneumatic drive includes a linear actuator,for example, a drive motor 110, such as a stepper motor or encoded DCmotor or another electromechanical element that produces accurateincremental bi-directional movements. The drive motor is coupled to acam or a lead screw mechanism or other mechanism that outputs linearmotion. However, any linear actuator mechanism could be used, so long asits position is known and it has negligible hysteresis or backlash. Thedrive motor 110 is coupled to a reciprocating element 115 thatreciprocates within a gas reservoir 120. The reciprocating element 115,e.g., a bellows or piston, translates bi-directionally in one dimension.Thus, translation by a known distance results in a known volume change.The reciprocating element interfaces with a gas, typically air, in thegas reservoir 120 such that translation of the reciprocating elementincreases or decreases the gas volume in the gas reservoir by a knownamount. The reciprocating element 115 and gas reservoir 120 togetherform a syringe-like mechanism.

The gas reservoir 120 is in fluid communication with the gas-sidechamber 171. A gas conduit 178 may be provided to fluidly connect thegas reservoir 120 with the gas-side chamber 171, depending on theconfiguration of the overall pumping system. A vent valve 112 isprovided that can be opened to vent air in the gas reservoir to ambient.Momentarily opening the vent valve equilibrates the pressure in thereservoir 120 and connected space (gas conduit 178 and gas-side chamber171) to atmospheric pressure. Any suitable vent valve can be used, suchas an electromechanical solenoid valve. A pressure sensor 155, such asany suitable pressure transducer, is also provided to measure thepressure within the gas reservoir 120, which also provides a measure ofthe pressure in the gas-side chamber and the fluid-side chamber of thepumping chamber.

A system controller 150 is provided in operative communication with themotor 110 and the vent valve 112 and with the pressure sensor 155 toreceive pressure data. The controller 150 includes a processor ormicroprocessor or the like and support electronics for communication,sensing, computation, and actuator control. The controller 150 includesnon-volatile memory (e.g., ROM) for storage of data and instructions,volatile memory (e.g., RAM) for input and output, a clock, and aninput/output (I/O) control unit. The controller 150 can be provided as amicrocontroller unit on a single chip. The controller can also interfacewith another computer or controller that is part of an overall pumpingsystem or pumping application, discussed further below.

The drive motor 110 is moved in known increments based on commands fromthe controller 150, which in turn moves the reciprocating element 115 aknown length to achieve a known change in gas volume in gas reservoir120. The volume change, in turn, results in a change in pressure inreservoir 120. The gas pressure seen at reservoir 120 and gas conduit178 is equilibrated with the gas pressure within the gas-side chamber171 and imposes the same pressure within the fluid-side chamber 172 byflexing of the flexible membrane 175, as there is no differentialpressure across the membrane.

In one embodiment, the reciprocating element 115 of the linear actuatoris formed as a bellows capable of controllable linear translation in onedimension. One end of the bellows is sealingly fixed to a rigid housingforming the gas reservoir 120 via, for example, a flange, and the otherend of the bellows is coupled to the motor 110 for linear movement, via,for example, a flange or an end plate. Thus, the diameter orcross-sectional area of the bellows is effectively fixed and thereforeknown. The interior of the bellows is open to and forms part of the gasreservoir. Accordingly, when the bellows translates linearly, generallyin a direction orthogonal to the plane of the end plate of knowndiameter, the volume change can be determined from the length oftranslation multiplied by the cross-sectional area of the bellows. Thelength of translation is known, because it is determined by theincremental motion of the drive motor, which is controlled by thecontroller 150.

Implementation of the reciprocating element as a bellows isadvantageous, because the bellows is capable of linear translationwithout stiction or friction against a housing. The bellows can bedesigned and fabricated with a known stroke length and spring rate andoperating pressure range on both sides of the bellows. Any suitablematerial, such as stainless steel or another metal alloy, for example, atitanium alloy, can be used in forming the corrugations of the bellows.Suitable bellows are commercially available from, for example,BellowsTech, LLC, of Florida.

In another embodiment, the reciprocating element of the linear actuatoris formed as a piston. The piston is coupled to the motor for lineartranslation within a cylinder that is coupled to or a part of the gasreservoir 120. The diameter or cross-sectional area of the piston endface (or cylinder) is fixed and known. Thus, as with the bellows, whenthe piston translates linearly, the volume change can be determined fromthe length of translation multiplied by the known, fixed cross-sectionalarea of the piston end face. The length of translation is known, becauseit is determined by the incremental motion of the drive motor, which iscontrolled by the controller 150. The linear actuator can also refer toan array of pistons, connected to a single drive motor. Various linearor rotary configurations of pistons can be used, for example, to meetpackaging requirements.

The controller 150 can adjust pressure in three ways. To createincreasing gauge pressure within the gas reservoir 120 by the linearactuator 115, which is then communicated to the gas-side chamber 171 andthen to the fluid-side chamber 172, the controller 150 can move motor110 in one direction, for example, clockwise. To create decreasing gaugepressure within the gas reservoir 120 by the linear actuator 115, whichis then communicated to the gas-side chamber 171 and then to thefluid-side chamber 172, controller 150 can move motor 110 in theopposite direction, counterclockwise. To produce zero gauge pressurewithin the gas reservoir 120, which is then communicated to the gas-sidechamber 171 and then to the fluid side reservoir 172, the controller 150can activate the vent valve 112.

By way of an overview, in operation to perform a FILL step, the ventvalve 112 is closed and the linear actuator 115 is retracted, whichincreases the volume and decreases the pressure in the gas reservoir 120and gas-side chamber 171. The pressure in the fluid-side chamber 172 issimilarly decreased, which leads to a pressure differential across theinlet valve 135. When the pressure differential reaches the crackingpressure of the inlet valve, the valve opens and fluid, primarilyliquid, from the fluid source flows through the inlet valve into thefluid-side chamber, in a FILL step. To perform a DELIVER step, the ventvalve is closed and the linear actuator is advanced. The pressure in thegas-side chamber and the fluid-side chamber increases, which leads to apressure differential across the outlet valve 145. When the pressuredifferential reaches the cracking pressure of the outlet valve, thevalve opens and liquid from the fluid-side chamber flows through theoutlet valve to the fluid sink, in a DELIVER step.

Referring now to FIG. 2, the controller 150 uses minimal inputs andoutputs to achieve flow control for the system. A point along the travelof the linear actuator 115, a “home” or “park” position, is stored instorage 321. Maximum and minimum travel positions of the linear actuatorduring FILL and DELIVER steps are stored as well. Periodic measurementsare made by the pressure sensor 155 and transmitted as a pressure signal322 to the controller 150. Motor control signals 324 are transmitted tothe motor drive 110 to move in either direction and over a wide range ofspeeds. The vent valve 112 is normally closed and can be openedprogrammatically via vent control signals 325. The controller alsoincludes a clock 326 for timing.

Commands from another controller or a host processor 380 from, forexample, an overall pumping system, can be exchanged digitally, forexample, via serial communication link 323. Only a small number ofsupported commands and queries are needed. The communication link canuse a common protocol such as Wi-Fi (IEEE 802 wireless standards), I2C,SPI, ZigBee, USB, TCP/IP, BTLE, or other protocols. The use of a highlevel, simple communications system allows for simplified softwarearchitecture and a more reliable verification process. The othercontroller 380 can reside on a mobile device, such as an iPhone, or atablet device, such as an iPad, which contains a program or application(app) for receiving data from and transmitting instructions to thesystem controller 150.

FIG. 3 shows various states and the association with positions of thelinear actuator 115. The linear actuator 115 can be moved by the motor110 under control of the controller 150 to any position. Certainpositions along the entire stroke are described as follows. Thepositions PARK 811 (the “home” position), MAX (or MAX PISTON) 812 (theposition at which the linear actuator is fully retracted during apumping cycle), and MIN 815 (or MIN PISTON) (the position at which thelinear actuator is least retracted (or fully advanced) during a pumpingcycle) are fixed positions by design. The position POS CRACKING 813(when the outlet valve opens) and position NEG CRACKING 814 (when theinlet valve opens) are variable, depending upon the conditions of theinfusion. The controller 150 includes instructions that maintain thesystem in one of several states, which determine the movement of thelinear actuator 115 and the interpretation of the pressure signal 322.When idle, the system is in the state UNLOCK 821 and the linear actuatoris brought to the position PARK 811. Upon instruction to begin aninfusion (which may be transmitted by the host processor 380), thecontroller 150 enters the state TO MIN 822 and the linear actuator 115is brought to the position MIN 815 with the vent valve 112 open. Oncethe infusion begins, the controller 150 enters the state CHANGE NEG 823and with the vent valve closed, the linear actuator 115 is graduallymoved (retracted) until the inlet valve 135 opens at the position NEGCRACKING 814. The state FILL 824 begins, during which the fluid-sidereservoir 172 fills with liquid from the source, and continues until thefluid-side reservoir 172 reaches its maximally filled position. Inpreparation to deliver fluid to the fluid sink 140, the controller 150moves the linear actuator 115 to the position MAX 812 with the ventvalve 112 open in the state TO MAX 825. The controller 150 enters thestate CHANGE POS 826 and with the vent valve closed, the linear actuator115 is gradually moved (advanced) until the outlet valve 145 opens atposition POS CRACKING 813. Finally, the linear actuator 115 advances ata speed to deliver the proper amount of fluid in the state DELIVER 827.When the state DELIVER 827 is complete, the controller 150 reverts backto the state TO MIN 822, continuing the cycle until the set target iscomplete.

The reservoir 120 with connected dead space of the gas conduit 178 andthe pumping chamber 175 has a finite volume. The linear actuator 115 hasa finite length of travel and can reach the limits of its position ineither direction. If the controller 150 seeks an increase in pressurewhen the linear actuator 115 is at position MIN 815, then it must movethe linear actuator towards position MAX 812 while the vent valve 112 isopen. The use of the vent valve allows movement of the linear actuatorwithout the generation of any pressure changes. Once the position MAX812 is reached, then the vent valve 112 is closed and the linearactuator is moved towards the position MIN 815, reducing the effectivevolume of the reservoir 120 and increasing the pressure of the gas-sidechamber 171. Similarly, if the controller 150 seeks a decrease inpressure when the linear actuator 115 is at the position MAX 812, thenit must move the linear actuator towards position MIN 815 while the ventvalve 112 is open. Once the position MIN 815 is reached, then the ventvalve 112 is closed and the linear actuator is moved towards theposition MAX 812, increasing the effective volume of the reservoir 120and decreasing the pressure of the gas-side chamber 171. With the ventvalve closed, the displacement of the linear actuator 115 from theposition MAX 812 to the position MIN 815 creates a change in volume anda subsequent change in pressure large enough that it exceeds thecracking pressure of the outlet valve. With the vent valve closed, thedisplacement of the linear actuator 115 from the position MAX 812 to theposition MIN 815 creates a change in volume and a subsequent change inpressure large enough to exceed the cracking pressure of the outletvalve. Similarly, with the vent valve closed, the displacement of thelinear actuator from the position MIN to the position MAX creates achange in volume and a subsequent change in pressure large enough toexceed the cracking pressure of the inlet valve.

FIG. 4a depicts a portion of FIG. 1 illustrating an air eliminationsystem (AES) 200 that forms part of the fluid control system 100. FIG.4b depicts a detailed view of the elements of the air elimination system200. Air bubbles 201 are shown within the fluid-side chamber 172, whichis in direct contact with a hydrophobic filter 202. The other side ofthe hydrophobic filter communicates via a conduit 203 with a one wayvalve 204, such as a check valve, leading to atmosphere.

In the course of filling and emptying the fluid side chamber 172, airbubbles 210 can enter fluid side chamber 172, for example, as a resultof out-gassing, making new fluidic connections, emptying fluid sourcecontainers, and the like. The fluid delivery comprises repeated cyclesof filling and emptying the fluid-side chamber 172 by imposing negativeand positive pressures in gas side chamber 171, allowing the flexiblemembrane 175 to freely move without differential pressure beingdeveloped. At the completion of a filling phase, negative pressure hasbeen applied to the gas-side chamber 171 and to the fluid-side chamber172, drawing fluid in from the fluid source 130 until such time thatflexible membrane 175 hits a mechanical limit imposed by the chamber170. Following the activation of the vent valve 112, the controller 150issues a command to the motor 110 to move the actuator 115 forward,reducing the volume of gas reservoir 120. The resultant pressure changeis measured, as discussed further below.

The cracking pressure of the outlet valve 145 must be substantiallyhigher than the cracking pressure of one way valve 204. In thecircumstance where air bubbles 201 are present and in surface contactwith the hydrophobic filter 202 and where pressure in the fluid-sidechamber 172 is greater than in the conduit 203, air bubbles 201 freelytravel across the hydrophobic filter 202 until such time as there is nodifferential pressure across the hydrophobic filter 202. When gaugepressures in the conduit 203 are higher than the cracking pressure ofthe one way valve 204, air travels through the open one way valve intoatmosphere. When the one way valve closes, the residual pressure in theconduit equals the cracking pressure of one way valve. Liquid isprevented from leaving or entering the system by virtue of the physicalproperties of the hydrophobic filter 202. Air from the atmosphere isprevented from entering the system due to the mechanical property of theone way valve 204.

In the filling phase of the system in which pressures in the fluid-sidechamber 172 are negative, a small amount of air trapped and pressurizedin the conduit 203 may re-enter the fluid-side chamber 172, serving topush or clear away a liquid barrier from the surface of the hydrophobicfilter 202. This small amount of air is an insignificant volume relativeto the fluid-side chamber 172, but does represent a regurgitation ofvolume that insignificantly reduces the efficiency of the pumpingsystem. The clearing of the filter is, however, useful especially forlong term infusions of colloidal suspensions, lipids, and other fluidswith strong surface tension properties.

The air filter 202 and one way valve 204 can be located in any suitablelocation in the fluid-side chamber 172. In one embodiment, they arelocated in a rigid wall of the housing and vent gas to ambient. Inanother embodiment, they are located within the membrane 175 and ventgas into the gas-side chamber 171, discussed further below.

In one embodiment, the fluid control system is implemented as twosubsystems. One subsystem encompasses the fluid administration set 102,incorporating the pumping chamber 170, including the gas-side chamber171 and the fluid-side chamber 172, the membrane 175, and the inlet andoutlet valves 135, 145. The fluid administration set can be disposableand can be maintained in a sterile condition. Tubing can be included asa part of the subsystem if desired, either attached to or attachable tothe inlet and outlet valves.

The other subsystem encompasses the pneumatic drive 101, which can bereadily connected to the fluid administration set 102 via the conduit178 from the gas reservoir 120 to the gas-side chamber. The conduit 178can be of any length, for example, up to 40 feet or more. With a conduitof greater length, the fluid administration subsystem can be removedfrom the vicinity of the pneumatic drive subsystem, which can beadvantageous in some situations. For example, some patients are inimminent need of both an infusion of fluids and an MRI (magneticresonance imaging) to, for example, detect internal bleeding. However,the electronics of most infusion pumps prevents these pumps fromoperating in the vicinity of the MRI equipment. Thus, these patientsmust either delay the MRI until a necessary infusion is complete, ordelay the infusion until the MRI is complete. The fluid administrationsubsystem 101 of the present fluid control system, however, contains noelectronics and can be used in the vicinity of MRI equipment. Thus, byemploying a conduit of a suitably long length, the fluid administrationsubsystem can be displaced a distance from the pneumatic drive subsystem102 and can be taken into the vicinity of the MRI equipment, allowingthe infusion to the patient to continue while the patient receives theMRI.

In one embodiment, referring to FIGS. 5a-12b , the fluid administrationsubsystem 102 is implemented as a removable, and if desired, disposable,cassette that is supported by a housing that, in turn, interfaces withthe pneumatic drive 102. The cassette 210 creates a sterile pathway fromthe fluid source 130 to the fluid sink 140, i.e., the vasculature of apatient. A housing 260 interfaces with and retains the cassette 210 inplace so that pressure can be conveyed to the membrane 175 from thepneumatic drive 102. The housing 260 creates an airtight interferencefit with a cassette top 222, connecting an air sealing ring 212 withpositive and negative air pressure connected to a pneumatic connection261. Gas pressure generated in the linear actuator 115 is connected tothe pneumatic connection 261 in the pump housing 260. When coupled withthe cassette inserted into the pump housing, as shown in FIG. 5b , anairtight seal is created between the pneumatic connection 261 and theair sealing ring 212. The flat surface of the cassette top thatinterfaces with the housing 260, along with the pneumatic connection 261that communicated from the linear actuator to the gas-side chamber 171,provide surfaces that can be readily kept clean and disinfected.

Referring to FIG. 4, the cassette 210 includes a rigid molded cassettebody 220 that forms a sandwich configuration with a rigid plate cassettebottom 225 and with the flexible membrane 175. The membrane 175 is ahighly flexible, impermeable feature of the cassette 210, separating theinterior of the body into the fluid-side reservoir 172 and the gas-sidereservoir 171, as discussed above. A gas filter 216 is secured into thecassette body 220. The inlet valve 135 and the outlet valve 145 areassembled into cassette body 220, oriented in such a way that fluid flowcan only proceed from an inlet tube 180 towards an outlet tube 190. Theinlet valve 135 is a one-way valve in the fluid path allowing flow fromthe source 130 to pumping chamber 170 defined by the cassette body 220and the cassette bottom 225, after its cracking pressure is reached.

The membrane 175 and the cassette bottom 225 are bonded to the cassettebody 220 to create a leak-free and sterile fluid pathway. An air checkvalve 215 is assembled into the cassette body 220, and the cassette top222 is bonded to the cassette body 220. A Bypass screw 265 providesmanual opening of the flow between the inlet tube 180 and the outlettube 175 and provides for manual enablement of fluid flow when thecassette 210 is removed from the system. The air sealing ring 212 isattached to the cassette top 222 above the cassette sealing surface 221.

FIG. 7a shows a cross-sectional view of the cassette 210. Gas pressurecommunicates through the gas sealing ring 212 and the cassette sealingsurface 221. The pressure is normally blocked by the gas check valve 215and communicates via a pneumatic pathway 227 to the gas-side reservoir171. The membrane 175 separates driving gas pressure from the fluid,which sits in the fluid side-reservoir 172. The cassette body 220,cassette top 222, and cassette bottom 225 provide fluid tight sealedpathways. The bypass screw 265 normally blocks free flow between theinlet tube 180 and the outlet tube 190. The gas filter 216 sits betweenthe fluid-side reservoir 172 and the gas check valve 215. FIG. 7b showsa cross-sectional view of the inlet valve 135 and the outlet valve 145.

Referring to FIG. 7a , the membrane 175 creates a fluid/gas barrier.Fluid occupies the fluid-side reservoir 172, between the inlet valve 135and the outlet valve 145, which are each one-way valves, allowing flowof fluid in only one direction from inlet tube 180 to outlet tube 190.The fluid held in the fluid-side reservoir 172 is kept segregated fromthe gas-side reservoir 171 via the membrane 175. If the membrane 175 isflexible and freely moving, then the differential pressure across themembrane is negligible. The fluid, while sitting in fluid side reservoir172, is in contact with a gas filter 216, for active air elimination, asdescribed above.

Referring to FIG. 7b , the inlet valve 135 and the outlet valve 145 aresymmetrical, both serving as passive check valves on either side of thefluid-side chamber 172. From the fluid-side chamber 172, fluid can bedriven by positive pressure through the outlet valve 145 to outlet tube190, leading to the fluid sink 140. The entire pathway 131 from thesource 130 to the sink 140 is sealed and sterile.

FIG. 8 is a cross section of the inlet valve 135. The geometry andfunction of the outlet valve 145 can be identical, so the same elementsapply. The inlet valve 135 is assembled onto the cassette body 220, andthen the membrane 175 and cassette bottom 225 are bonded to the cassettebody 220 to create a fluid tight seal. Fluid 50 communicates freely witha proximal valve chamber 235. Valve flow channels 237 provide a pathwayto a distal valve chamber 236, but the inlet valve 135 prevents flow offluid because it is sealed at a valve seat 234. A gap is formed andfluid flows at the valve seat 234 from the proximal valve chamber 235 tothe distal valve chamber 236 when the pressure differential pressureforces exceed the valve force 242. The valve force 242 is determined bythe relative position of a valve retainer 233 and the valve seat 234.The flow of fluid exits the distal valve chamber 236 via the valve inletchannel 238, entering fluid-side reservoir 172.

Referring to FIG. 8, the fluid 50 comes from inlet tube 180 and sits inproximal valve chamber 235, unless the differential pressure, ascompared to distal valve chamber 236, is high enough to offset valveforce 242 and cause the inlet valve 135 to open. When the inlet valve135 opens, fluid travels through valve flow channels 237, across valveseat 234 and into distal valve chamber 236. In conditions where pressureis relatively negative in the fluid-side chamber 172, the fluid travelsthrough the valve inlet channel 238.

Pressure in the fluid side reservoir 172 is communicated via the valveinlet channel 238 to the distal valve chamber 236. If pressure in thedistal valve chamber 236 is greater than pressure in the proximal valvechamber 235, the forces at the valve seat 234 are increased and theinlet valve 135 remains closed to fluid flow. If pressure in the distalvalve chamber 236 is less than pressure in the proximal valve chamber235, the forces at the valve seat 234 are decreased and inlet valve 135opens to fluid flow. The force required to open the inlet valve 135 atthe valve seat 234 depends on the valve force 242, which for any givenmaterial, is a function of the distance between the valve retainer 233and the valve seat 234. Increasing the gap between the valve retainerand the valve seat increases the valve force, requiring a higherdifferential pressure between the proximal valve chamber 235 and thedistal valve chamber 236 to open the inlet valve 135. The function ofthe outlet valve 145 can be identical to that of inlet valve 135.

In many pumping applications, the check valve function is attempting tohave perfect sealing against reverse flow and minimal forward pressureon the order of 2 inches of water required for full flow. In the presentfluid control system, the forward cracking pressures are purposefullyhigh, on the order of 30 inches of water or 1 PSId. This high crackingpressure translates into a substantial dimensional interference at thevalve seat 234 and a substantial valve force 242, so that themanufacturing tolerances of the interfering parts do not developsubstantial variation in cracking pressures.

FIG. 9 shows a close up cross-sectional view of the center portion ofthe cassette 210. Positive gas pressure is communicated through the gassealing ring 212, via the cassette sealing surface 221, and upon the gascheck valve 215. Gas valve flow channels 245 are blocked by the gascheck valve 215 and no flow can enter towards the fluid-side reservoir172. A certain level of negative gas pressure can distort the gas checkvalve 215, allowing flow through the gas valve flow channels 245 fromthe fluid-side reservoir 172 towards the cassette sealing surface 221.Flow of liquid is stopped by the special physical properties of the gasfilter 216, which is interposed between the fluid-side reservoir 172 andthe cassette sealing surface 221. The gas filter 216 is formed of ahydrophobic material that allows the flow of gas therethrough but notthe flow of liquid. The pressure needed to open the gas check valve 215and allow flow through the gas valve flow channels 245 is thedifferential pressure between the cassette sealing surface 221 and thefluid-side reservoir 172. Since the membrane 175 is freely moving, thepressure in the gas-side reservoir 171 is effectively identical to thatin the fluid-side reservoir 172.

The fluid 50 is, in practice for an infusion to a patient from a medicalpump, a combination of air (the gas) and liquid. Especially during aninitial priming function or when changes are made to the sourcecontainer, quantities of air can appear in the fluid-side chamber 172.During the states CHANGE NEG 823 and FILL 824, negative gauge pressuresare created by the linear actuator 115. These negative pressures areseen at the cassette sealing surface 221 and the top of the gas checkvalve 215. If the fluid-side chamber 172 contains air that is touchingthe surface of the gas filter 216, then flow of air can travel from thefluid-side chamber 172 to the cassette sealing surface 211 via the gascheck valve 215. Unlike the inlet valve 135 and the outlet valve 145,which each have relatively high cracking pressures, the gas check valve215 has a relatively low cracking pressure and opens easily. If air iscontained within the fluid-side chamber 172, but is not touching thesurface of the gas check valve 215, then it remains in fluid-sidechamber 172. The requirement for detecting this residual air is stillimportant, even though, in most circumstances, an unlimited amount ofair can be removed.

FIG. 10 shows a close up view of the construction of the cassette 210 inthe vicinity of the air filter 216. The gas check valve 215 is insertedinto the cassette body 220 from the top. The gas filter 216 is fittedinto a gas filter seat 252. Fluid sits on top of the membrane 175 in thespace of the fluid-side reservoir (not shown in FIG. 10) and exits viathe valve outlet channel 253. Fluid enters the fluid-side reservoir 172via the valve inlet channel 238. FIG. 10b shows the relationship of thegas check valve 215, the cassette body 220, and the gas filter 216 asassembled.

While the ability to infuse accurately over a wide flow rate range,monitor conditions, and remove air bubbles are useful features of thepresent system, there may be times when manual control of fluid flow isrequired. FIGS. 11a and 11b illustrate one form of bypass valve 265which can open a bypass channel 267 between the inlet tube 180 and theoutlet tube 190. The bypass channel 267 is a feature in the cassette 210which creates a flow path from proximal to the inlet valve 135 to distalof the outlet valve 145. It is normally closed by the bypass valve. Thebypass valve includes a screw 266 that fits within an internallythreaded aperture 269 in the cassette body 220. The screw can be rotatedby a handle 271 protruding from the cassette body 220. An opening 268 isformed through the screw. FIG. 11a shows the bypass valve rotated intothe open position, in which the opening 268 is aligned with the channel267, allowing fluid to flow through the cassette. FIG. 11b shows thebypass valve rotated 90° into the closed position, in which the opening268 is not aligned with the channel 267. Fluid flow is blocked from thechannel 267 and diverted to the inlet valve 135.

FIG. 12a is an exploded view of the cassette 210. Gas pressurecommunicates through the gas sealing ring 212 and the cassette sealingsurface 221 before traversing to a pneumatic pathway 272 in the cassettebody 220. A membrane gas passthrough 276 in the membrane 175 allows gasto reach a bottom gas pathway 278 in the cassette bottom 225. The bottomgas pathway 278 communicates to the gas-side chamber 171, allowing thegas pressure to impinge upon the membrane 175 and communicate to thefluid-side chamber 172. FIG. 12b is a top view of the cassette body 220,showing the pneumatic pathway 272. Also visible is the valve outletchannel 281.

A primary requirement of any intravenous pump is to prevent a runawayoverinfusion to a patient when the administration set is removed fromthe pump. The cassette 210 is retained in its relationship to pumphousing 260 until the controller 150 goes to the state UNLOCK 821. Theuser can then remove the cassette 210 from the pump housing 260 andpressure is removed from the gas-side chamber 171. The head height ofthe source 130 is limited by the total tubing length of the inlet tube180 and the outlet tube 190, so the driving pressure is limited to lessthan 2 PSIg. The inlet and outlet valves 135, 145 operate in series,each with a cracking pressure on the order of 1 PSI, for a totalcracking pressure of 2 PSI. In normal application, the driving pressureis far less than 2 PSI, so flow reliably stops and is never in a freeflow condition.

One benefit of high cracking pressure check valves is the requirement ofsignificant positive and negative pressures to achieve fluid flow. Thecessation of fluid flow to the sink can be achieved by simply relievingthe driving pressure. Activation of the vent valve 112 immediately stopsfluid flow through the outlet valve 145. While there may be some storedcapacitance in the outlet tube 190 that continues to discharge into thesink 140, that value is small due to the typically low operatingpressures of system.

FIG. 13 illustrates an embodiment of a failsafe circuit. The ventfunction is made redundant by the addition of a vent backup valve 512.Activation of either vent 112 or vent 512 reduces the gauge pressure ofthe gas-side chamber 171 to zero and fluid flow stops. The vent valve112 is activated by a digital logic circuit of the controller 150 duringnormal operation. The vent backup valve 512 is operated by capacitivedischarge that is held in abeyance by a pulse every second from thecontroller 150, in response to a regular communication from the hostprocessor 380. If host processor 380 does not successfully communicatewith the controller 150 or if the controller 150 is incoherent, then thepulse is not issued to hold up the capacitive discharge and the ventbackup valve 512 is activated, even in the event of a total power loss.The vent backup valve 512 can be activated routinely by withholding thepulse, to test the proper operation of vent backup valve 512.

Control of the fluid system is described with more particularity asfollows. The measurements made during an infusion can be used todetermine the following:

a) amount of liquid delivered to the sink (patient);

b) amount of air in the fluid line;

c) source fluid pressure;

d) source fluid impedance;

e) sink (patient) line pressure;

f) sink (patient) line impedance;

g) verification of motor movement; and

h) verification of vent function.

Even though there are a substantial number of characteristics of thefluid flow environment for the system, there are only three parametersto examine, from which all the information is inferred. The pressuresignal 322 measures absolute pressures under a query from the controller150. The second parameter is the position of the linear actuator 115.The use of a stepper motor and home switch provides for an accuratemeasurement of the linear actuator. Time is the third parameter. Eventhough the effective flow rate of the system depends on the pressuredeveloped in the reservoir 120 and connected gas-side chamber 171, thecontroller 150 is not attempting to maintain a certain driving pressure.Pressure generation is a dependent variable in the system.

Each step of the motor provides a known and constant change in gasvolume in the system. The resultant change in absolute pressure providesa measurement of the total gas volume. Thus, each step of the motorgives an indication of the fluid volume at any point in time. Changes influid volume over time provide an indication of the flow rate. When thereciprocating element is advanced, the pressure driving the fluid firstincreases and then decreases as fluid leaves the system and “leaks” intothe sink. This is illustrated as a stepped or sawtooth shape on a graphof pressure vs. time. (See, for example, FIG. 16.) The change inpressure provides a real time proportional signal related to the fluidflow rate.

The controller uses the ideal gas law to perform many calculations. Theideal gas law states:PV=nRTwhere: P is the absolute pressure of the gas, and is measured by thepressure sensor;

V is the volume of the gas and is determined by the number of motorsteps;

n is the number of moles of gas in the volume and is unchanged here;

R is a universal gas constant; and

T is the absolute temperature.

The controller compares measurements of pressure and volume at differenttimes:P ₁ V ₁ /n ₁ R ₁ T=P ₂ V ₂ /n ₂ R ₂ T ₂In this system, n1=n2 and R1 =R2 and the absolute temperature T1 and T2are effectively unchanged in the time intervals measured. The volumes V₁and V₂ are the total gas volumes in the reservoir 120, in the cassetteand in dead space such as the conduit between the reservoir 120 and thechamber 170. The volume of the reservoir can be determined bycalculation. The volume of the dead space is unchanging, and the totalcontained volume in the cassette is invariant. Thus, the change inliquid volume in the cassette can be computed from this relationship.The pressures P₁ and P₂ are the measured pressures at two times, whichmay be before and after a volume change. Thus, the relationship becomes:P₁V₁=P₂V₂

Pressure signals collected via pressure transducer 155 demonstrate thechanges in pressure in gas reservoir 120 under various conditions.Pressure within the gas reservoir 120 can change under three conditions:first, if the actuator 115 moves within the gas reservoir 120 andchanges the gas volume; second, if fluid leaves the fluid-side chamber172 via the outlet valve 145 to the fluid sink 140; and third, if fluidenters the fluid-side chamber 172 via the inlet valve 135 from the fluidsource 130.

Referring to FIG. 14, a pressure response to a known volume reduction(e.g., by moving the reciprocating element 115 a known distance) isshown at A. The pressure is sensed before and after the known decreasein volume, while both the inlet and outlet valves are closed. Signal Ais used in calculations leading to a measurement of total gas volume. Anexample of the calculation of a total gas volume at a time t₁ is asfollows:

The effective surface area A of the actuator, e.g., a bellows or piston,is fixed at, for example, 1.3 cm². The actuator is moved by the motorfrom an initial displacement position D_(init)=1 cm to a final positionD_(final-1)=2 cm. The volume change V_(change) while both the inlet andoutlet valves are closed can then be calculated as the area times thedistance moved:

$\begin{matrix}\begin{matrix}{V_{change} = {A\left( {D_{init} - D_{{final} - 1}} \right)}} \\{= {1.3\mspace{14mu}{{cm}^{2}\left( {{1\mspace{14mu}{cm}} - {2\mspace{14mu}{cm}}} \right)}}} \\{= {{- 1.3}\mspace{14mu}{cm}^{3}}}\end{matrix} & (1)\end{matrix}$The pressure when the actuator is at D_(init) is measured to beP_(init)=15 psi, and when the actuator is at D_(final) is measured to beP_(final-1)=20 psi. The initial volume V_(init) at time t₁ is thencalculated as follows:

$\begin{matrix}{{V_{init} = \frac{\frac{V_{ch}P_{final}}{P_{init}}}{1 - \frac{P_{final}}{P_{init}}}}{V_{init} = {5.2\mspace{14mu}{cm}^{3}}}} & (2)\end{matrix}$

As noted above, the change in pressure of fluid in the fluid-sidechamber is equivalent to the change in gas pressure in the gas-sidechamber. Thus, the fluid volume change can be calculated by calculatingthe total gas volume at two different times using Equations 1 and 2above. For example, at time t₂, the actuator is again moved 1 cm for avolume change V_(change-2)=−1.3 cm³. The pressures before and aftermoving the actuator are measured to be P_(init)=15 psi andP_(final-2)=19.5 psi. Using Equation 2, the total gas volume iscalculated to be 5.63 cm³. The difference between the gas volumes at t₁and t₂ is:5.65 cm³−5.2 cm³=0.43 cm³This value is used to increment the cumulative delivered volume. Knowingthe fluid volume change, the amount of fluid delivered to the fluid sinkcan be accurately monitored using only the pressure measurementscoordinated with the known incremental linear movements of the actuator.

Referring to FIG. 15, a pressure response when vent valve 112 is openedis shown as B1. (The pressure returns to 0 PSIg.) A pressure response toa known volume increase is shown as B2 (the vent valve having beenclosed). Signal B2 is used in calculations leading to a measurement oftotal gas volume, for example, during a fill cycle, as described in theexample above. The pressure is measured both before and after theincreased displacement.

FIG. 16 illustrates a pressure response to individual incrementalmovements of the actuator 115, which progressively decreases the gasvolume and increases pressure, because the outlet valve is closed. Thepressure increase is shown as D. Note that the pressure at D remainsunchanged between motor moves, as indicated in the enlarged view of D.Once a sufficient pressure is reached, the outlet valve opens, shown atC, and a pressure decay is measured. As fluid is delivered through theoutlet valve, calculations for motor timing are made as indicated in thefollowing example and referring to FIG. 17.

Motor constants are given as follows, based on the geometry of the gasreservoir 120 of the system:

MOT_(mcl)=17.3 μL

MOT_(stroke)=88

VOL_(del)=0 μL

MOT_(mcl) is a calculated constant based on the effective surface areaof the bellows or piston times the linear displacement of a single step.MOT_(stroke) is the number of motor steps taken in a nominal FULLDELIVERY cycle. In FIG. 17, the solid line is the target rate ofinfusion (VOL_(tgt)/SEC_(tgt)). The dotted line indicates the actualrate of infusion during the elapsed time from START TIME until TIME NOW(VOL_(del)/SEC_(elp)). The dashed line is the calculated rate ofinfusion to meet the target rate. The computation of the target volume,VOL_(tgt), the amount of liquid to be delivered at the end of the nextfull stroke, is:VOL_(tgt)=VOL_(del)+(MOT_(mcl)*MOT_(stroke))The time elapsed since the start of the infusion, SEC_(elp), (inseconds) is computed as follows:SEC_(elp)=TIME NOW−START TIMEwhich can be converted from mL/hour to μL/sec if necessary as follows:

${{RATE}\left( {{µL}\text{/}\sec} \right)} = \frac{1000*{{RATE}\left( {{ml}\text{/}{hr}} \right)}}{3600\mspace{14mu}\sec\text{/}{hr}}$The time (in seconds) at which the target volume should be completed,based on the target flowrate, is computed as follows:SEC_(endstroke)=VOL_(tgt)/RATE(μl/sec)The time in which the next stroke should be complete to achieve thetarget (in sec) is computed as follows:SEC_(stroke)=SEC_(endstroke)−SEC_(elp)The time, MOT_(btwsteps), between motor steps (converted to msec) toachieve the rate is computed as follows:MOT_(btwsteps)=SEC_(stroke)*1000/MOT_(stroke)

The system is also capable of responding to various conditions thatoccur during an infusion. For example, FIG. 18 illustrates a possiblepressure response when the hydrostatic pressure of fluid sink 140 ischanged. Pressure pattern E indicates a reduction in the pressure. Oncethe system detects the reduction shown by pattern E, the system respondsto increase the pressure, indicated by pressure pattern F, which showsthe pressure increasing.

FIG. 19 shows a pressure response when the impedance of the flow intothe fluid sink 140 is changed. Pressure pattern G illustrates pressurechanges that indicate that the sink impedance is increased. Pressurepattern H illustrates pressure changes that indicate that the sinkimpedance is reduced.

The system can distinguish between impedance changes and changes in sinkpressure. Referring to FIG. 20, a pressure rise is detected, indicatedby J. The movements of the actuator 115 are then slowed to better seethe baseline pressures, shown at K. In this instance, the baselinepressure does not rise, providing an indication that the pressure riseseen at J results from increased impedance of the fluid flow.

Operation of the controller 150 is further described with moreparticularity as follows. The parameters measured or calculated by thecontroller 150 are set out in the following Table:

TARGET VOL (μL) Amount of liquid in microliters to be delivered; i.e.,the target volume of liquid to be delivered TARGET TIME (sec) Number ofseconds in which to deliver TARGET VOL START TIME Timestamp of wheninfusion begins OWED VOL (μL) Volume of liquid remaining in thescheduled infusion DELIVERED VOL (μL) Volume of liquid measured to havebeen delivered to the sink STROKE VOL (μL) Amount of gas contained inknown displacement of linear actuator, i.e., volume displaced by astroke of the linear actuator TARGET STROKE TIME Time at which nextSTROKE VOL should be delivered (msec) MOTOR STEPS Number of motor stepstaken for complete STROKE VOL STEP TIME (msec) Timing between motorsteps DELIVERED VOL FULL Amount of complete STROKE VOL delivered, i.e.,cumulative volume of liquid delivered; incremented after each stateDELIVER DELIVERED VOL INTERIM Portion of a single STROKE VOL delivered,i.e., the volume delivered in an ongoing state DELIVER; reset to 0 aftereach state DELIVER is completed MOTOR COUNT Number of MOTOR STEPS taken

The host processor 380 sends to the controller 150 (or the controllercalculates based on user inputs) two variables. TARGET VOL is ameasurement of microliters of liquid to be delivered to the fluid sink140 over a period of TARGET TIME starting from the time of thecommunication, START TIME.

Measurement of DELIVERED VOL, the volume of liquid delivered to thesink, is a primary parameter for calculating the target delivery, TARGETVOL. There are two components to this measurement, the first beingDELIVERED VOL FULL, the tally of completed states of the state DELIVER827. The second component, DELIVERED VOL INTERIM is the estimate offluid delivered in the midst of a single ongoing state DELIVER 827. Onceeach state DELIVER 827 has been completed, DELIVERED VOL INTERIM is setto zero and DELIVERED VOL FULL is incremented. Over multiple cycles, theaccuracy of DELIVERED VOL INTERIM becomes less relevant, although stillimportant for low flow rates which may deliver a single STROKE VOL overmany hours. DELIVERED VOL INTERIM may be computed in two ways. Undermost conditions, the number of steps taken during the state DELIVER 827,the MOTOR COUNT divided by MOTOR STEPS provides a good estimate of thepercentage completion of STROKE VOL. For example:

If MOTOR COUNT=100,

MOTOR STEPS=400, and

STROKE VOL=1,000 μl,

then DELIVERED VOL INTERIM=(100/400)*1000=250 μL.

The controller 150 invokes another precision volumetric method tocompute DELIVERED VOL INTERIM at flow rates substantially below 5 mL/hr.This measurement should be made on the order of every 10 minutes, so asto eliminate effects of ambient temperature or pressure changes. Insteadof the normal single increment of MOTOR COUNT, the controller 150directs the motor 110 to conduct ten reverse steps, followed by tenforward steps, bringing the linear actuator 115 back to its originalposition. The reason for making multiple steps with a net zero change indriving pressure is to provide a large pressure signal, needed for ahigh resolution volume measurement. Recordings of the pressure signal322 are made at a frequency on the order of 1,000 Hz and stored foranalysis. Ideal gas law calculations are used to compute the remainingvolume of the fluid-side chamber 172, as described above. Subtractingthat volume from the volume at the state FILL 824 provides a value forDELIVERED VOL INTERIM that is not subject to drift or signal to noiseratios.

Referring to FIG. 3, positive pressure generation to move fluid acrossthe outlet valve 145 to the sink 140 is done during only one state, thestate DELIVER 827. Assume, for the moment, that the membrane 175 is in aposition so that the fluid-side chamber 172 is at a maximum value and isfully filled with liquid and that the gas-side chamber 171 is at aminimum value. Assume also that linear actuator 115 is in the positionPOS CRACKING 813. At this point of control, any steps forward of thelinear actuator 115 actually deliver fluid the fluid sink. (See alsopoint C in FIG. 16.) The controller 150 has moved from the state CHANGEPOS 826 to the state DELIVER 827.

At the initiation of the state CHANGE POS 826, the controller 150computes a value for OWED VOL, calculated by:OWED VOL=(NOW−START TIME)*(TARGET VOL/START TIME)The controller 150 keeps track of the volume delivered to the sink,DELIVERED VOL.

The system is designed with a fixed STROKE VOL. To achieve a flow rateerror of zero, within the resolution of measurements, the next STROKEVOL should be delivered in TARGET STROKE TIME (converted to msec),calculated by:

${{TARGET}\mspace{14mu}{STROKE}\mspace{14mu}{TIME}} = \frac{\left( {{{DELIVERED}\mspace{14mu}{VOL}} - {{OWED}\mspace{14mu}{VOL}} + {{STROKE}{\mspace{11mu}\;}{VOL}}} \right)}{{TARGET}{\mspace{11mu}\;}{VOL}*{TARGET}\mspace{14mu}{TIME}\text{/}\left( {1000\mspace{14mu}{msec}\text{/}\sec} \right)}$The motor drive has a well-defined mechanical linkage, such that thenumber of steps to achieve STROKE VOL is exactly known as MOTOR STEPS.The timing between MOTOR STEPS is STEP TIME, as calculated by:STEP TIME=TARGET STROKE VOL/MOTOR STEPS

EXAMPLES

reference FLOW RATE mL/hr 60 60 60 6 600 value reference DURATION min120 120 120 120 240 value sample data NOW 13:30:00 13:30:00 13:30:0013:30:00 13:30:00 sample data START_TIME 12:30:00 12:30:00 12:30:0012:30:00 12:30:00 sample data TARGET VOL (μL) 120,000 120,000 120,00012,000 2,400,000 sample data TARGET TIME 7,200 7,200 7,200 7,200 14,400(sec) calculated OWED VOL (μL) 60,000 60,000 60,000 6,000 600,000 sampledata DELIVERED VOL 60,000 59,500 61,000 5,990 600,000 (μL) referenceERROR % 0.00% −0.83% 1.67% −0.17% 0.00% value sample data STROKE VOL(μL) 1,000 1,000 1,000 1,000 1,000 sample data MOTORSTEPS 400 400 400400 400 calculated TARGET STROKE 60,000 30,000 120,000 594,000 6,000TIME (msec) calculated STEP TIME (msec) 150 75 300 1,485 15

During the state DELIVER 827, the motor drive operates forward everyTARGET STROKE TIME. If the fluid is leaving the fluid-side chamber 172at the same rate as the gas-side chamber 171 volume is changing, thenthere is no change in driving pressure of the fluid.

If the flow of fluid towards the sink is slower than the volume changein the gas-side chamber 171, then the driving pressure increases,causing the flow rate to increase, causing a concurrent increase in flowrate. Similarly, if the flow of fluid towards the sink is faster thanthe volume change in the gas-side chamber 171, then the driving pressuredecreases, causing the flow rate to decrease, causing a concurrentdecrease in flow rate.

Following the final step of STROKE VOL, the controller 150 pauses untila pressure signal from the pressure sensor indicates that the outletvalve 145 is closed until moving from the state DELIVER 827 to the stateTO MIN 822.

The computation of STEP TIME, the time between steps, is made at thebeginning of each state DELIVER 827, so that any delays which occurduring any of the other states are automatically compensated for. Duringthe state DELIVER 827, the fixed delivery speed creates an automaticadjustment of driving pressure, within limits, to adjust to changingenvironmental conditions.

The described system and method represent a simplified computationalscheme that works over a large flow rate range. In addition, the systemis operable to determine various operating conditions based on pressuredata and trends and can provide a notification or alarm to a user ifnecessary.

Referring to FIG. 21, the pressure signals 322 are recorded and analyzedduring state CHANGE NEG 823 and state FILL 824 to provide informationabout various conditions. Information about the fluid source 130 can bediscovered by examining the various features of the pressure signals,including the pressure trend 881 before the FILL state commences. Anormal cracking pressure of the inlet valve is indicated at 882 and anormal FILL pressure trend is indicated at 883. A high cracking pressurefor the inlet valve is indicated at 884. A low cracking pressure isindicated at 885. If air enters the chamber, the pressure responseappears as shown at 886. A high impedance in the fluid source isindicated by the trend 887. A pressure response due to stiction followedby release, for example, for a syringe source, is indicated at 888 and889.

Referring to FIG. 22, the pressure signals 322 are also recorded andanalyzed during state CHANGE POS 826 and state DELIVER 827. Informationabout the fluid sink 140 can be discovered by examining the variousfeatures of the pressure signals, including the pressure trend 891before the DELIVER state commences and a normal pressure trend 892before the outlet valve opens. A normal cracking pressure of the outletvalve is indicated at 893 and a normal DELIVER pressure trend once theoutlet valve opens is indicated at 894. A high cracking pressure for theoutlet valve is indicated at 895. A low cracking pressure is indicatedat 896. If air is present, the pressure response appears as shown at897. A pressure response indicating a disconnect is indicated at 898. Animpedance is indicated at 899.

Even though the system provides a mechanism to actively remove air fromthe fluid, it does not remove the obligation to measure the presence ofair, so that mitigating action can be taken by the user. Assume that thestate FILL 824 is complete because volume measurements during the stateFILL 824 have confirmed that the gas-side chamber 171 is at its minimumvalue. After the controller 150 directs the linear actuator 115 to theposition MAX 812 in the state TO MAX 825, it moves to the state CHANGEPOS 826. A certain number of steps is made, such that a large pressurechange is seen, but not enough to open the outlet valve 145. Using thesame ideal gas law calculations described above, the total gas volume iscalculated and compared to the expected gas volume at the initiation ofthe state DELIVER 827. Residual gas in the gas-side chamber 171 appearsas an incremental total gas volume.

The total gas volume is calculated when the fluid-side chamber iscompletely filled with liquid. The area A of the actuator, e.g., abellows or piston, is fixed at, for example, 1.3 cm². The actuator ismoved by the motor from an initial position D_(init)=1 cm to a finalposition D_(final-1)=1.2 cm. The volume change V_(change) while both theinlet and outlet valves are closed can then be calculated as the areatimes the distance moved:

$\begin{matrix}\begin{matrix}{V_{change} = {A\left( {D_{init} - D_{{final} - 1}} \right)}} \\{= {1.3\mspace{14mu}{{cm}^{2}\left( {{1\mspace{14mu}{cm}} - {2\mspace{14mu}{cm}}} \right)}}} \\{= {{- 0.26}\mspace{14mu}{cm}^{3}}}\end{matrix} & (1)\end{matrix}$The pressure when the actuator is at D_(init) is measured to bep_(init)=15.000 psi, and when the actuator is at D_(final) is measuredto be p_(final-1)=17.000 psi. The initial volume V_(init) at time t₁ isthen calculated as follows:

$\begin{matrix}{{V_{init} = \frac{\frac{V_{ch}p_{final}}{p_{init}}}{1 - \frac{p_{final}}{p_{init}}}}{V_{init} = {2.210\mspace{14mu}{cm}^{3}}}} & (2)\end{matrix}$

The same calculation done when the chamber contains a 50 μL air bubbleis as follows. At time t₂, the actuator is again moved 1 cm for a volumechange V_(change-2)=−0.26 cm³. The pressures before and after moving theactuator are measured to be p_(init)=15 psi and p_(final-2)=16.950 psi.Using Equation 2, the total gas volume is calculated to be 2.260 cm³.The difference between the gas volumes at t₁ and t₂ is:

$\begin{matrix}{{{2.260\mspace{14mu}{cm}^{3}} - {2.210\mspace{14mu}{cm}^{3}}} = {0.05\mspace{14mu}{cm}^{3}}} \\{= {50\mspace{14mu}{µL}}}\end{matrix}$

The simplicity of this measurement demonstrates another benefit of highcracking pressure check valves, providing a significant quiescent periodbetween filling and delivery of the fluid-side chamber 172.

A secondary measurement of air ingress into the fluid-side chamber 172is made during the state FILL 824. In a liquid filled column, each motorstep generates a specific pressure change. The instant that air hits theinlet valve 135, the flow resistance changes by an order of magnitudeand the pressure changes diminishes greatly. This measurement of airingress need not be quantitative, but it serves as a flag to indicatethat the subsequent air measurement is important. Referring to FIG. 21,the pressure response at 886 shows the characteristic pressure changesseen during air ingress.

Measuring the hydrostatic pressure of the source 130 is useful. It canoften be a determinant of the remaining liquid in a flexible bag hangingabove the pump. Upon completion of the state DELIVER 827, the state TOMIN 822 begins, leading to the state CHANGE NEG 823. Increasing negativegauge pressure is developed during the state CHANGE NEG 823 with eachmotor step. The controller 150 is monitoring the pressure after eachmotor move to determine a time when the pressure begins to become lessnegative at the position NEG CRACKING 814, indicating the opening of theinlet valve 135. The pressure at which the inlet valve opens varies withthe pressure of the source. The differential cracking pressure of theinlet valve 135 depends upon the valve force 171, which is high. Thatoffset does not, however, prevent the measurement of pressure at thesource with high resolution. The valve force 171 is a value roughlyknown by design and represents pressure at the position NEG CRACKING814. If the source has a head height of zero, then the inlet valve 135opens at the expected pressure based only on the valve force 171. If theposition NEG CRACKING 814 happens at a less negative pressure, then thesource head height can be calculated as a positive head heightdifferential. The actual value of the source head height can only bedetermined if the host processor 380 exploits its user interface todirect the operator to place the source at an exact head height. Evenwithout quantitative information, the source pressure can be roughlycalculated and can be tracked with as much precision as the controller150 circuitry allows, for example, to a fraction of an inch of water.

It can useful to roughly measure the impedance or resistance to flowfrom the source during the state FILL 824. This use of the sourceimpedance is the recognition of an upstream occlusion. One of the uniqueproperties of the system is its ability to fill the fluid-side chamber172 completely even in the presence of a partial upstream occlusion. Itmay take a relatively long time to complete the state FILL 824 and thatwould take a toll on the maximum achievable flow rate, but the filledcondition of the fluid-side chamber 172 is measured, not assumed. Duringthe state FILL 824, the motor 110 moves at a constant rapid speed,producing a continuous change in negative pressure seen in the reservoir120. The slope of this pressure change is a direct measurement of theimpedance of the fluid as it drags across the inlet valve 135. As notedabove, FIG. 21 shows examples of different resistances to flow. A highresistance caused by a viscous fluid would show a steep, continuousslope, as shown at the pressure response 887. Erratic frictional forcesfrom a source incorporating a syringe would show high slopes interruptedby low slope segments during movement of the syringe plunger as shown atthe stiction pressure response 888 followed by the release pressureresponse 889.

Measuring the hydrostatic pressure of sink 140 is useful. It can oftenbe a determinant of a downstream occlusion. Upon completion of the stateFILL 824, the state TO MAX 825 begins, leading to the state CHANGE POS826. Increasing positive gauge pressure is developed during the stateCHANGE POS 826 with each motor step. The controller 150 is monitoringthe pressure after each motor step to determine a time when the pressurebegins to become less positive at the position POS CRACKING 813,indicating the opening of the outlet valve 145. The pressure at whichthe outlet valve 175 opens varies with the pressure of the sink 140. Thecracking pressure of the outlet valve 175 depends upon the valve force171, which is high. That offset does not, however, prevent themeasurement of pressure at sink 140 with high resolution. The valveforce 171 is a value roughly known by design and represents pressure atthe position POS CRACKING 813. If sink has a head height of zero, thenthe outlet valve 174 opens at the expected pressure based only on thevalve force 171. If the position POS CRACKING 813 happens at a lesspositive pressure, then the sink head height can be calculated as anegative head height differential. The actual value of the sink headheight can only be determined if the host processor 380 exploits itsuser interface to direct the operator to place the sink at an exact headheight. Even without quantitative information, the sink pressure can beroughly calculated and can be tracked with as much precision as thecontroller 150 circuitry allows, for example, to a fraction of an inchof water.

The measurement of output impedance is not as straightforward as it isfor the input described above. Each motor movement during the stateDELIVER 827 increases the driving pressure and, so long as the pressureof the fluid-side chamber 172 is enough to open the inlet valve 170, apressure decay can be measured using the pressure signal 322. During thestate DELIVER 827, pressure immediately following each motor step can berecorded for a relatively short period on the order of 100 msec. FIG. 23shows a method of data sampling during flow during a step of the motorwhen the resistance of the outlet valve 175 is at it minimal value. Theslope of fluid flow can be easily measured from the pressure post trendindicated at 854. The pressure decay, shown by the pressure post trend854, can be scaled by the pressure differential between the pressurepost intercept 855 and at the position POS CRACKING 813 indicated at852. This measurement provides a calculation of total output impedance,which includes the sum total of resistance across the outlet valve 145,flow resistance of outlet tube 190, flow resistance of any connections,catheters that are interposed between outlet valve 145 and thevasculature of the patient. Significant changes in the output impedancecan be suggestive of a clinical problem. Referring again to FIG. 22, thepressure deliver impedance indicated at 899 illustrates a high level ofpatient resistance. The pressure response disconnect indicated at 898illustrates the opposite condition of low resistance and low pressure,likely due to a line disconnection.

More particularly, using the ideal gas law, the instantaneous flow ratecalculation is made routinely, for example, on the order of once persecond, by analyzing the trend of pressure signals 322 transmitted bythe pressure sensor. A single value for pressure is derived from anarray of samples taken on the order of 1 KHz, so as to analyze thesignals for noise.

Referring again to FIG. 23, the pressure signal 322 is recorded before,during, and after each movement of the reciprocating element 115 at timeintervals indicated at 851 during a DELIVER step (state DELIVER 827).Subsequent measurements are analyzed for the pressure post trend,indicated at 854, and the pressure post intercept value (also calledP_(f) in the calculations below), indicated at 855, is derived from thistrend. The pre motor step pressure, indicated at 852, (also called P_(i)in the calculations below) is compared to pressure post intercept value855 using the ideal gas law. The post motor step peak pressure signal,indicated at 853, which is recorded immediately after the movement ofthe reciprocating element 115, is a thermal artifact form adiabaticcontraction that is not included in the calculation.

Assume for this example the following:

Total stroke volume=1,500 μL (fixed by the system)

Steps per total stroke=400 (fixed by the system)

Volume per step in stroke=1,500 μL/400 steps=3.75 μL

Also assume for this example that the reciprocating elements moves 5steps (e.g., from motor step position 140 to motor step position 135).The volume displaced by these 5 steps is:5 steps*3.75 μL/step=18.75 μLThe volume at the beginning is known from a previous calculation(correct?) and can be taken as, for example, 525.00 μL. The final volumedisplacement due to this movement is calculated as:525.00 μL−18.75 μL=506.25 μLThe initial pressure p_(i) is measured as 15.00 PSIa. The derived finalpressure p_(f) is 15.22. Thus, from the ideal gas law comparison, thesystem volume V_(n) of gas at time n is determined as follows:(V _(n) +V _(i))*P _(i)=(V _(n) +V _(f))*P _(f)V _(n) *P _(i) −V _(n) *P _(f) =V _(f) *P _(f) −V _(i) *P _(i)V _(n)*(P _(i) −P _(f))=V _(f) *P _(f) −V _(i) *P _(i)V _(n)=(V _(f) *P _(f) −V _(i) *P _(i))/(P _(i) −P _(f))Thus:V _(n)=((506.25 μL*15.22 PSIa)−(5.25 μL*15.00 PSIa))/(15.00 PSIa−15.22PSIa)=772.2 μL

The fluid control system and method described herein are advantageousfor a variety of reasons. The system combines the simplicity of a directdrive pump with the high level of sensitivity of a pneumatic drivesystem by providing a pneumatically coupled, direct drive infusioncontrol system. The system is based on gentle air pressure and is easierto use. Traditionally, pumps have used powerful mechanical elements todeform tubing or move syringes to expel fluid flow from within thesestructures. The present direct drive mechanism has the advantage of asimple control algorithm in which a drive motor is advanced in knownincrements with a known stroke volume. Faster flow rates have shorterintervals between motor pulses.

Traditional infusion pump architectures diminish the sensitivity to theunderlying fluid flow going to the patient and potentially expose thepatient to high pumping pressures. In a tubing pump, for example, theforce required to crush the tubing to an occluded state is far largerthan the force required to move the fluid. The present system, however,takes the advantage of a simple direct drive mechanism, yet offers theability to measure the fluid flow outcome and have increased sensitivityto the environmental factors. This concept applies relatively lowpressures, similar to or less than those seen with a gravity infusion,to the fluid and the observation of fluid flow can be observed directly.A thin non-permeable membrane separates the driving air pressure fromthe fluid being delivered and the net force on the membrane approacheszero. The membrane is formed so that no stretching forces are seen bythe membrane; it translates freely on one axis in response to anydifferential pressure, for example, like a loudspeaker.

A precision reciprocating element is moved via a linear actuator, e.g.,stepper motor and a precision lead screw or other volume displacementmechanism. The precision from each of the components is inherent in themanufacturing process and does not add cost to the system design. Themotor is advanced at an interval that is a function of the targeted flowrate. Each step provides a new measurement of fluid volume and eachmeasurement in between steps provides a change in pressure proportionalto fluid flow. In this way, a single measurement system is used in twoways to measure flow rate.

At very low flow rates, the pressure changes are small and eventuallyrun into a signal-to-noise issue. This noise includes environmentalchanges of temperature and atmospheric pressure. If the single movementof the reciprocating element results in a pressure greater than desired,then an alternative strategy can be employed to measure air volume.Rather than advance the reciprocating element, the reciprocating elementcan be withdrawn several steps and then returned to the originalposition, resulting in no net pressure increase. This “net zero”perturbation of air volume can be as large as needed to provide a largesignal, well above the noise floor.

Another advantage of the present system is that it allows for animproved strategy for fluid delivery accuracy. Traditionally, a largevolume infusion pump will drive a motor mechanism to achieve a certainflow rate. Any errors in this delivery will be additive over time. Thepresent system provides for automatic compensation for delays that arepredictable, such as the time to fill the fluid chamber from the sourceand for errors that are not predictable, such as a temporary and partialupstream occlusion.

The control provided by the present system is based on a desireddelivery of discrete fluid volumes over time, rather than a constantflow rate. Even if the user expresses a desire to go at a flow rateindefinitely, that can easily be expressed as a series of volume overtime sequences. For example, to the system, a request for 60 mL/hourcould appear as 60,000 microliters over 3,600 seconds or 600,000microliters over 36,000 seconds.

The present system is operable to deliver a known stroke volume and,advantageously, to measure the actual volume in a fluid chamber at thebeginning and end of each stroke delivery. At a fixed point in thecontrol algorithm, the system determines at what future time thecompletion of the next complete stroke volume is due. Once this time isdetermined, the dwell between steps in the motor to complete the strokeis easily calculated and the pump proceeds with virtually nocomputational overhead. Delays from any source, predictable or not, areautomatically compensated for and errors in flow rate do not contributeto longer term inaccuracies.

Still another advantage of the present system resides in its ability toprovide a short term, self-regulating fluid flow control strategy.Traditionally, the creation of a closed loop control system mightrequire a sophisticated and complex control system. This complexitycould lead to problems with reliability and with excessive powerconsumption. The architecture of the flow control system herein allowsfor the benefits of a timer-based open loop pumping system (simplicity)and the benefits of a closed loop control system (accuracy andresponsiveness).

Since the system herein accurately measures liquid volume delivered tothe patient and accurately measures time, the amount due the patient atany instant in time can be measured. For example, in certainembodiments, following every FILL cycle of the fluid chamber, thecalculation is made of the time desired to empty the chamber. The timebetween steps is calculated internally. If, for example, the nominalflow rate is 2 mL to be delivered over 60 seconds and the pump startsthis cycle in debt to the patient of 0.2 mL, then the normal 2.0 mLcycle should be shortened by approximately 10% or should be completed in54 seconds. Since the number of steps required to displace 2.0 mL isprecisely known, the time between steps is easily determined.

Following a FILL cycle, there is no flow out to the patient until theoutlet valve cracking pressure has been met. The calculations of timingare made at the moment that the outlet valve cracking pressure is metfollowing a FILL. This method intrinsically accounts for the intra-cycledelays with no need for complex control calculation.

At the end of an EMPTY cycle, there is sustained flow out to the patientuntil the driving pressure falls below the outlet valve crackingpressure. The FILL cycle is delayed until this point in the pressuredecay. This method intrinsically accounts for the intra-cycle delayswith no need for complex control calculation. If the pump is runningbehind in its rate, then the steps will happen more rapidly and thedelivery pressure will intrinsically increase, causing the rate to catchup to the desired rate. This requires no control code at all to makethis pressure adjustment. If the pump is running ahead in its rate, thenthe steps will happen less rapidly and the delivery pressure willintrinsically decrease, causing the rate to slow down to the desiredrate. This requires no control code at all to make this pressureadjustment.

A measure of post-fill high compliance provides an indication of one oftwo conditions. Air may have entered the system from the source.Alternatively, the fill cycle may have been incomplete, as would occurwith an occluded inlet or fully evacuated non-vented supply container.The ambiguity of the signal for high compliance can be resolved withrepeated fill cycles. Ultimately, even if the problem is unresolved, itleads to the exact same outcome, namely, the cessation of pumping and anotification, such as an alarm, a text message to a user, or like.

Yet another advantage of the present system resides in its ability tomeasure source fluid pressure and flow resistance as well as sink fluidpressure and flow resistance without additional sensors. Conventionalfluid flow controllers are often equipped with multiple pressuretransducers which are situated in a way to record the hydrostaticpressure of the source fluid and of the patient line. This methodrequires separate pressure transducers, careful coupling of the fluid,and, usually, a poor sensitivity of measurement because the fluid ismeasured across a relatively thick barrier which imposes its own set offorces. The present system measures source fluid pressure and sink linepressure using a single pressure sensor of the system and offers nocomplexities in the disposable interface to the pump. This measurementcomes at essentially no cost and offers nearly perfect sensitivity. Thepressure measurement is subject to a significant offset error, but mostof the known clinical considerations for an infusion pump are based ontrends, rather than absolute values.

The value of pressure and impedance measurements has a combinatorialeffect. For example, a source with low pressure and one with high andvariable impedance is likely to be a syringe. Another example would be asource of low impedance and steadily decaying source pressure is likelyto be a soon-to-be empty fluid bag. A high patient line impedance andunchanging pressure may indicate a kinked tube. Another example would bea low impedance in the patient line and a reduction in patient linepressure, indicating a likely patient line disconnection. Havingknowledge of the source fluid and patient line is an importantingredient for a reliable infusion system.

The system is described herein as a basic system, although systems withadded functionality are also contemplated. The fluid control systemimplements a pneumatically coupled direct drive mechanism that can beintegrated as a subassembly into a finished medical product thatincludes additional components or subassemblies, such as a chassis, apower supply, a user interface, clinical information management, and thelike.

In a conventional fluid coupled syringe pump, a slight movement of thepiston is displacing incompressible liquid, so the instantaneouspressure change is a function of the downstream compliance, includingthe syringe wall, the tubing, various connectors, and fluid flow losses.In the present system, a step movement of the reciprocating elementincreases the air pressure, proportional to the rest of the air space inthe reservoir and attached space. For example, a 10-microliter movementof the piston into a total gas space of 1,000 microliters will increasethe driving pressure by 1% of atmospheric pressure or merely about 0.15PSI. This pneumatic coupling solves the impedance mismatch problem ofprior art pumping systems mentioned above.

The gas pressure is readily measured with a single precise andcalibrated pressure sensor. Instead of using a complex routine whereactive switching valves combine an unknown gas volume with a known gasvolume, so that a computed gas volume can be determined, the presentsystem uses the relationship between a reciprocating element movementand a change in volume. A known motor displacement results in a knownvolumetric displacement, so the resultant gas pressure measurementsresult in a calculated gas volume. The absence of a separate measurementsequence results in significant improvement over the prior art, becausevalves, a control chamber, and related calculations are no longerrequired. The act of generating gas pressure, either positive ornegative, also provides a measurement of gas volume. The pumping phaseand measurement phase are unified.

The gas pressure is imposed upon a flexible membrane, with a mechanicalconfiguration that creates negligible forces throughout its entirestroke volume. This configuration could include features such as a thinwall and molded-in curvatures, similar to those found commonly in aso-called “rolling sock” diaphragm. Alternatively, the membrane can bethermoformed to the shape of the housing. Therefore, a gas pressure of1.0 PSI, for example, imposes a nearly identical pressure on the otherside of the membrane which is exposed to the sterile fluid pathway. Thedifferential pressure is very low and known by design. This flexiblemembrane solves one of the problems with peristaltic pumps in theirability to accurately and sensitively read pressures through therelatively thick wall of an extruded tubular pumping segment.

Alternating air pressure, created by the gas reservoir coupled to thereciprocating element, imposes positive and negative gauge pressures onthe liquid side of the membrane. Inlet and outlet check valves proximaland distal to this central membrane create a unidirectional pumpingaction. The system utilizes a pair of passive fluid check valves withpurposefully high cracking pressures, for example, on the order of 1PSId. The passive check valves are an improvement over designs thatutilize active valves. The high cracking pressure of the check valvesmakes for a very reliable design; there is a tradeoff with low crackingpressure and reliability of sealing. Most check valves in the IV therapymarket seek to have a cracking pressure measured in a few inches ofwater, whereas the present system operates an order of magnitude higher.All infusion devices must incorporate a method of preventing “free flow”when the tubing set is removed from the pump mechanism. The combinedcracking pressure of the in-series inlet and outlet check valves servesthis “flow stop” purpose with no additional mechanism, component, orcomplexity.

The liquid side stroke volume of the membrane is on the order of 1 mL.The stroke volume of the reciprocating element is about double that,providing the ability to generate positive and negative pressures duringthe period when both check valves are shut and then still have thestroke capacity to match the liquid side stroke volume. In order toaccommodate all ranges of flow and pressure, there are times when thereciprocating element must be moved to a certain location withoutgenerating any pressure on the membrane. The vent valve is used toeliminate pressure on the membrane during such movements. The cost,power consumption, and control logic of the vent valve is negligible.During operation, flow can be stopped with the activation of the ventvalve. In certain embodiments, a failsafe design can incorporate aredundant vent valve that is activated by control electronics in theabsence of an “ALL OK” control signal, although other fail safe designsare also contemplated.

The control system can be designed to integrate with other components,such as a chassis and user interface, to create a finished medicaldevice. The control system can incorporate commercially available parts,including a microcontroller, a bellows or a syringe-likecylinder/piston, a linear actuator motor/gear, a pressure transducer,and a vent valve. Custom embedded controller software, as describedherein, can provide the control based on requests from a host computerthat is part of the finished medical device. The user interface,communications, and control logic of the host computer that determinesthe targeted fluid flow rate are common to all infusion pumps on themarket and can be encompassed within the scope of embodiments of thepresent fluid control system.

The present system can employ a cassette-like configuration that isincorporated into a finished IV administration set that containselements both proximal and distal to the cassette, such as a dripchamber, tubing, secondary tubing connections, injection ports, and Luerconnectors. The cassette offers a leak free fluid path, a passive inletcheck valve with, for example, approximately 1 PSId cracking pressure, ahighly flexible membrane with, for example, an approximate 1 mL strokevolume, and a passive outlet check valve with, for example,approximately 1 PSId cracking pressure. In one embodiment, the crackingpressure for each valve is at least 0.5 PSId.

The present system can be embodied in a module designed for large volumeinfusion pumps, wherein the module herein can be connected to avirtually unlimited source of fluid from bags or bottles or multiplesyringes. This is in contrast to small volume pumps that dispense only afinite amount of contained fluid, such as a syringe pump or disposableambulatory pump.

The disposable subsystem of the present system may be spliced into aconventional “gravity administration set,” which is a typicalconfiguration for a large volume IV pump.

The pumping subsystem of the present system is an electromechanicalsubassembly that may be adapted for incorporation by a pump manufacturerinto a complete infusion pump product. The subassembly herein mayadvantageously be configured as a single off-the-shelf subassembly toreplace a pump's existing mechanical architecture including doors,lever, motors, cams, springs, and drive electronics.

The present system is described herein primarily by way of reference toa flow control system for IV therapy; however, it will be recognizedthat the present system may be adapted for moving all manner of fluids,including enteral feeding devices and other non-medical applications.

Various system and process aspects of the invention are contemplated,including the following:

A fluid control system or process for delivery of a fluid including acontroller in communication with a pressure sensor to receive sensedpressure data and in operative communication with a pneumatic drive tocontrol incremental volume changes based on the sensed pressure data andon a predetermined fluid delivery schedule.

A fluid control system or process wherein the controller is operable todecrease a volume of gas in communication with a gas-side chamber,whereby pressure in a fluid-side chamber also decreases until a crackingpressure of an inlet valve is reached, whereupon the inlet valve opensand fluid from the fluid source enters a fluid-side chamber.

A fluid control system or process wherein the controller is operable toincrease a volume of gas in communication with a gas-side chamber,whereby pressure in a fluid-side chamber also increases until a crackingpressure of an outlet valve is reached, whereupon the outlet valve opensand fluid in the fluid-side chamber exits to the fluid sink.

A fluid control system or process wherein the controller is operable tocontrol delivery of liquid to a fluid sink by determining a volume ofliquid to be delivered as the difference between a target volume ofliquid to be delivered and a volume of liquid already delivered andoperating the pneumatic drive in increments calculated to deliver thevolume of liquid to be delivered.

A fluid control system or process wherein the controller is operable tocalculate the volume of liquid to be delivered at successive timeintervals and update the volume of liquid already delivered after eachcalculation of the volume of liquid already delivered.

A fluid control system or process wherein the controller is operable to:

-   -   receive sensed pressure data before and after a controlled        movement of a pneumatic drive,    -   compare the pressure data to a known change in gas volume        resulting from said controlled movement, and    -   calculate a volume of gas based on the pressure data and the        known change in gas volume based on an ideal gas law        relationship between the sensed pressure data and the known gas        volume.

A fluid control system or process wherein the controller is operable torepeat the calculation of a volume of gas based on the pressure data andthe known change in gas volume over multiple times during delivery of aliquid to the fluid sink such that accumulated rate errors areeliminated from accuracy errors.

A fluid control system or process wherein the controller is operable toexert a negative pressure on a gas reservoir in fluid communication witha gas-side chamber separated from a fluid-side chamber by a flexiblemembrane to draw liquid from the fluid source into the fluid-sidechamber through a one-way inlet valve until the fluid-side chamber fillswith fluid; exert a positive pressure on the gas reservoir in fluidcommunication with the gas-side chamber to deliver liquid in thefluid-side chamber to the liquid sink through a one-way outlet valve;monitor pressure in the gas reservoir during the steps of exerting thenegative pressure and exerting the positive pressure; and determinevolumes of fluid in the fluid-side chamber from incremental changes involume of the gas reservoir and the gas-side chamber and any connectingdead space by an ideal gas law relationship, wherein P₁V₁=P₂V₂, whereinP₁ and P₂ are pressures measured at two times before and after volumechanges and V₁ and V₂ are volumes at the two times.

A fluid control system or process wherein the controller is operable todetermine a pressure trend indicative of a hydrostatic pressure or animpedance or a resistance in the fluid flow path from the fluid source.

A fluid control system or process wherein the hydrostatic pressure orthe impedance or the resistance in the fluid source is indicative of atleast one of an occlusion in a line on the fluid flow path, an amount ofliquid remaining in the fluid source, a viscous liquid at the fluidsource, and a syringe.

A fluid control system or process wherein the controller is operable todetermine a pressure trend indicative of a hydrostatic pressure or animpedance or a resistance in the fluid flow path to the fluid sink.

A fluid control system or process wherein the hydrostatic pressure ofthe impedance or the resistance in the fluid flow path to the fluid sinkis indicative of at least one of an occlusion in a line on the fluidflow path and a disconnected connection to the fluid sink.

A fluid control system or process wherein the controller is operable todetermine a pressure trend indicative of air in the fluid flow path.

A fluid control system or process wherein the controller is operable todetermine a pressure trend indicative of a cracking pressure of an inletvalve or an outlet valve that is higher or lower than normal.

A fluid control system or process wherein the controller is operable todetermine a pressure trend indicative of a stiction and release due to asyringe.

A fluid control system or process wherein the controller is operable toenter various states to perform a pumping cycle, the states including anunlock state in which the system is ready to start a pumping cycle.

A fluid control system or process wherein the controller is operable toenter various states to perform a pumping cycle, the states includingmoving a reciprocating element of a pneumatic drive to a fully retractedposition of a pumping stroke.

A fluid control system or process wherein the controller is operable toenter various states to perform a pumping cycle, the states includingmoving a reciprocating element of a pneumatic drive to a fully advancedposition of a pumping stroke.

A fluid control system or process wherein the controller is operable toenter various states to perform a pumping cycle, the states includingretracting a reciprocating element of a pneumatic drive until a crackingpressure of an inlet is reached.

A fluid control system or process wherein the controller is operable toenter various states to perform a pumping cycle, the states includingretracting a reciprocating element of a pneumatic drive when the inletvalve is open and liquid fills a fluid-side chamber.

A fluid control system or process wherein the controller is operable toenter various states to perform a pumping cycle, the states includingadvancing a reciprocating element of a pneumatic drive until a crackingpressure of an outlet valve is reached.

A fluid control system or process wherein the controller is operable toenter various states to perform a pumping cycle, the states includingadvancing a reciprocating element of a pneumatic drive when the outletvalve is open and liquid is delivered from the fluid-side chamber.

A fluid control system or process wherein the controller is operable todrive a pneumatic drive in controlled steps, each step providing a knownvolume displacement of gas volume.

A fluid control system or process wherein the controller is operable todrive a pneumatic drive in controlled steps to deliver fluid through aone-way outlet valve, wherein with each step, pressure driving the fluidfirst increases and then decreases as liquid leaks through the outletvalve.

A fluid control system or process wherein the controller is operable todrive a pneumatic drive in controlled steps to deliver fluid through aone-way outlet valve, and to calculate a time between steps to achieve adesired rate of infusion.

A fluid control system or process wherein the controller is operable todrive a pneumatic drive in controlled steps to deliver fluid through aone-way outlet valve, and to monitor a pressure decay after eachincrease in driving pressure, and to calculate a pressure value derivedfrom the pressure decay.

A fluid control system or process wherein the controller is operable toreduce a volume of the gas reservoir by an amount that exerts a positivepressure on the gas reservoir in fluid communication with the gas-sidechamber such that the positive pressure is inadequate to deliver liquidin the fluid-side change to the liquid sink and to monitor pressure inthe gas reservoir during the steps of exerting the positive pressure.

A fluid control system or process wherein the controller is operable todetermine volumes of fluid in the fluid-side chamber from incrementalchanges in volume of the gas reservoir and the gas-side chamber and anyconnecting dead space by an ideal gas law relationship, whereinP₁V₁=P₂V₂, wherein P₁ and P₂ are pressures measured at two times beforeand after volume changes and V₁ and V₂ are volumes at the two times; todetermine a pressure trend from the step of monitoring the pressure overseveral time steps, and to monitor the pressure trend, the volumechanges, or both for an indication of air in the fluid-side chamber.

A fluid control system or process wherein the controller is operable todetermine an indication of air from a decrease in pressure during a stepof filling a fluid-side chamber.

A fluid control system or process wherein the controller is operable todetermine an indication of air from an increase in pressure during astep of delivering liquid that is below a normal pressure increaseduring the delivering step.

A fluid control system or process wherein the controller is operable toprovide a comparison of a gas volume when a fluid-side chamber is fullyfilled with liquid to a subsequent determination of a gas volume whenthe fluid-side chamber contains air to determine a presence of air inthe fluid-side chamber.

An infusion pumping system or process comprising a fluid flow controlsystem including a controller, and a host controller in communicationwith the controller of the fluid flow control system, the hostcontroller operable to receive instructions for determining a course ofan infusion, the instructions including one of a rate of infusion or avolume of liquid to be delivered over a determined time interval, theinstructions further including a start time.

An infusion pumping system including a user interface and a powersupply.

An infusion pumping system including a chassis, and wherein at least aportion of a fluid flow path of the fluid flow control system, includingan inlet valve and an outlet valve, and a chamber are supportable on thechassis.

It will be appreciated that the various features of the embodimentsdescribed herein can be combined in a variety of ways.

The present invention has been described with reference to the preferredembodiments. It is to be understood that the invention is not limited tothe exact details of construction, operation, exact materials orembodiments shown and described, as obvious modifications andequivalents will be apparent to one skilled in the art. It is believedthat many modifications and alterations to the embodiments disclosedwill readily suggest themselves to those skilled in the art upon readingand understanding the detailed description of the invention. It isintended to include all such modifications and alterations insofar asthey come within the scope of the present invention.

What is claimed is:
 1. A process for controlling an infusion of fluidfrom a fluid source to a liquid sink, comprising: a) exerting a negativepressure on a gas reservoir in fluid communication with a gas-sidechamber separated from a fluid-side chamber by a flexible membrane todraw fluid from the fluid source into the fluid-side chamber through aone-way inlet valve until the fluid-side chamber fills with fluid; b)exerting a positive pressure on the gas reservoir in fluid communicationwith the gas-side chamber by effecting a plurality of known, incrementalchanges in a volume of the gas reservoir as a series of discrete stepsto deliver fluid in the fluid-side chamber to the liquid sink through aone-way outlet valve, wherein the one-way inlet valve and one way outletvalve each are passively operated and only open when a pressuredifferential between an upstream fluid and a downstream fluid reaches apredetermined cracking pressure; c) monitoring pressure in the gasreservoir during the steps of exerting the negative pressure andexerting the positive pressure; and d) determining volumes of fluid inthe fluid-side chamber from the plurality of known, incremental changesin the volume of the gas reservoir and the gas-side chamber and anyconnecting dead space by an ideal gas law relationship, whereinP₁V₁=P₂V₂, wherein P₁ and P₂ are pressures measured before and aftervolume changes, respectively, and V₁ and V₂ are volumes before and afterthe volume changes, respectively.
 2. The process of claim 1, furthercomprising repeating steps a through d, and wherein a total volume offluid delivered to the liquid sink is determined after each successiverepetition of steps a through d by adding a calculated volume change toa previously determined total volume.
 3. The process of claim 1, whereinin step a, the negative pressure is exerted until the pressuredifferential across the one-way inlet valve reaches the predeterminedcracking pressure of the one-way inlet valve such that the one way inletvalve opens and fluid flows into the fluid-side chamber, and thenegative pressure is exerted additionally to continue drawing fluid intothe fluid-side chamber until the fluid-side chamber fills with fluid asdetermined by a volume determined in step d.
 4. The process of claim 1,wherein in step b, the positive pressure is exerted until the pressuredifferential across the one-way outlet valve reaches the predeterminedcracking pressure of the one-way outlet valve such that the one-wayoutlet valve opens and fluid flows out of the fluid-side chamber, andthe positive pressure is exerted additionally to continue deliveringfluid out of the fluid-side chamber until the fluid-side chamber isemptied of fluid as determined by a volume determined in step d.
 5. Theprocess of claim 1, wherein a volume of the fluid-side chamber and thegas-side chamber together is fixed and the volume of the gas reservoiris variable by a known and controlled amount using a reciprocatingelement and a bidirectional linear actuator.
 6. The process of claim 1,wherein a pressure trend is determined from the step of monitoring thepressure, and further wherein the pressure trend is indicative of one ormore conditions upstream of the fluid-side chamber, downstream of thefluid-side chamber, or both, the one or more conditions selected fromthe group consisting of one or more of: an indication of remaining fluidin the fluid source, air in the fluid-side chamber, an occlusion in anupstream line, an occlusion in a downstream line, and a disconnection inan output line.
 7. The process of claim 1, wherein a pressure trend isdetermined from the step of monitoring the pressure, and further whereinthe pressure trend is indicative of air in a fluid flow path.
 8. Theprocess of claim 1, wherein the negative pressure and positive pressureare exerted using a reciprocating element selected from the groupconsisting of: a bellows end coupled at one end to a linear actuator, aninterior of the bellows comprising at least part of the gas reservoir;and a piston reciprocable within a cylinder, the cylinder comprising atleast part of the gas reservoir.
 9. The process of claim 1, wherein instep d, sensed pressure data is received before and after each known,incremental change in volume of the gas reservoir, the sensed pressuredata is compared to a known change in gas volume resulting from saidknown, incremental change in volume of the gas reservoir, and a totalvolume of gas is calculated based on the sensed pressure data and theknown, incremental change in volume of the gas reservoir based on saidideal gas law relationship between the sensed pressure data and theknown, incremental change in volume of the gas reservoir.
 10. Theprocess of claim 1, further comprising: periodically determining a totalvolume of fluid delivered to the liquid sink; and repeating steps athrough d and until the total volume of fluid delivered to the liquidsink is equal to a predetermined target volume.
 11. The process of claim1, further comprising: periodically monitoring changes in a volume offluid delivered to the liquid sink over time to calculate a flow rate offluid delivered to the liquid sink; and adjusting a rate of effectingthe plurality of known, incremental changes in volume of the gasreservoir until the flow rate of fluid delivered to the liquid sink isequal to a predetermined target flow rate.